Differential inhibition of [ 3 H]-oxotremorine-M and [ 3 H]-quinuclinidyl benzilate binding to muscarinic receptors in rat brain membranes with acetylcholinesterase inhibitors

Lockhart, Brian P.; Closier, Matthieu; Howard, Katrina; Steward, Chelsea A.C.; Lestage, Pierre

doi:10.1007/s002100000382

Cited by 33 publications

(5 citation statements)

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“… References: a=[ 154 ] b=[ 155 ] c=[ 156 ] d=[ 157 ] e=[ 158 ] f=[ 159 ] g=[ 160 ] h=[ 161 ] i=[ 162 ] j=[ 163 ] k=[ 164 ] l=[ 165 ] m=[ 166 ] n=[ 167 ] o=[ 168 ] p=[ 169 ] q=[ 170 ] r=[ 171 ] s=[ 172 ] t=[ 173 ] u=[ 147 ] v=[ 174 ], w=[ 175 ] x=[ 176 ]. …”

Section: Fig (1)unclassified

Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment

Soukup

Winder

Killi

et al. 2017

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BackgroundPharmaceuticals with targets in the cholinergic transmission have been used for decades and are still fundamental treatments in many diseases and conditions today. Both the transmission and the effects of the somatomotoric and the parasympathetic nervous systems may be targeted by such treatments. Irrespective of the knowledge that the effects of neuronal signalling in the nervous systems may include a number of different receptor subtypes of both the nicotinic and the muscarinic receptors, this complexity is generally overlooked when assessing the mechanisms of action of pharmaceuticals.MethodsWe have search of bibliographic databases for peer-reviewed research literature focused on the cholinergic system. Also, we have taken advantage of our expertise in this field to deduce the conclusions of this study.ResultsPresently, the life cycle of acetylcholine, muscarinic receptors and their effects are reviewed in the major organ systems of the body. Neuronal and non-neuronal sources of acetylcholine are elucidated. Examples of pharmaceuticals, in particular cholinesterase inhibitors, affecting these systems are discussed. The review focuses on salivary glands, the respiratory tract and the lower urinary tract, since the complexity of the interplay of different muscarinic receptor subtypes is of significance for physiological, pharmacological and toxicological effects in these organs.ConclusionMost pharmaceuticals targeting muscarinic receptors are employed at such large doses that no selectivity can be expected. However, some differences in the adverse effect profile of muscarinic antagonists may still be explained by the variation of expression of muscarinic receptor subtypes in different organs. However, a complex pattern of interactions between muscarinic receptor subtypes occurs and needs to be considered when searching for selective pharmaceuticals. In the development of new entities for the treatment of for instance pesticide intoxication, the muscarinic receptor selectivity needs to be considered. Reactivators generally have a muscarinic M2 receptor acting profile. Such a blockade may engrave the situation since it may enlarge the effect of the muscarinic M3 receptor effect. This may explain why respiratory arrest is the major cause for deaths by esterase blocking.

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Section: Fig (1)unclassified

Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment

Soukup

Winder

Killi

et al. 2017

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“…Special attention should be given to knockout studies, which provide information about the number of receptors of specific subtypes. 3) Use the “specific” agonist and/or antagonist with respect to its pKi (see ( Pascuzzo et al, 1984 ; Cantí et al, 1998 ; Becerra et al, 2001 ; Lockhart et al, 2001 ; Samochocki et al, 2003 ; Harada et al, 2010 ; Alexander et al, 2017a ; Alexander et al, 2017b ; Myslivecek, 2019 ) and the IUPHAR/BPS Guide to Pharmacology ( www.guidetophamacology.org )). 4) Compare the subtype proportion and the effects of drugs.…”

Section: Discussionmentioning

confidence: 99%

“…3) Use the “specific” agonist and/or antagonist with respect to its pKi (see ( Pascuzzo et al, 1984 ; Cantí et al, 1998 ; Becerra et al, 2001 ; Lockhart et al, 2001 ; Samochocki et al, 2003 ; Harada et al, 2010 ; Alexander et al, 2017a ; Alexander et al, 2017b ; Myslivecek, 2019 ) and the IUPHAR/BPS Guide to Pharmacology ( www.guidetophamacology.org )).…”

Section: Discussionmentioning

confidence: 99%

“…Unavailable data are shown as blank spaces. Data are from or adapted from ( Pascuzzo et al, 1984 ; Cantí et al, 1998 ; Becerra et al, 2001 ; Lockhart et al, 2001 ; Samochocki et al, 2003 ; Harada et al, 2010 ; Alexander et al, 2017a ; Alexander et al, 2017b ; Myslivecek, 2019 ) and the IUPHAR/BPS Guide to Pharmacology ( www.guidetophamacology.org ). The activity represents the main effect of a specific ligand.…”

Section: Social Isolation and Cholinergic Mechanismsmentioning

confidence: 99%

“…Other morphological changes were also found ( Plaschke et al, 1987 ). The effects of galantamine (a weak competitive and reversible cholinesterase inhibitor that also acts as a potent allosteric ligand of human NRs α 4 β 2 , α 3 β 4 , and α 6 β 4 and mouse nAChRs α 7 /5-HT 3 ( Samochocki et al, 2003 ) and acts on MRs ( Lockhart et al, 2001 )) and donepezil (a cholinesterase inhibitor that interacts with both MRs and NRs) on prepulse inhibition deficits elicited by isolation rearing were studied by Koda et al (2008) . Galantamine, but not donepezil, attenuated prepulse inhibition deficits, which may favor the nicotinic effects of galantamine (the affinity of NRs to donepezil is lower than galantamine) for AChE inhibition.…”

Section: Social Isolation and Cholinergic Mechanismsmentioning

confidence: 99%

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Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

Mysliveček

2021

Front. Pharmacol.

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Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

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